In this application, it is postulated that the effects of gonadal steroids on immunity are mediated, at least in part, at the level of the thymus via thymocyte proliferation and programmed cell death. This proposal examines the role of androgenic hormones in thymic involution and the development of the immune repertoire. The four specific aims are to (1) define the cellular targets for androgen-induced thymocyte apoptosis; (2) define the cellular targets mediating androgen effects on tissue-specific proliferation; (3) interrupt intrathymic androgen signaling pathways and examine resulting immune system composition and function; and (4) define the role of TGF-b in the mediation of androgen-induced thymic involution.